The proposed research will continue investigations currently supported by N.I.H. Grant AM-11028. The contemplated investigations involve development of methods for cytochemical localization of specific substances by light and electron microscopy and application of newly developed or standard techniques to investigation of problems in normal cell biology and pathobiology. Efforts will be made to improve methods for visualizing mucosubstances for staining elastin at the ultrastructural level. Methods for immunostaining tissue antigens by light and transmission and scanning electron microscopy will be further investigated. These and other cytochemical methods will be applied to investigation of pathogenesis of human disease. Cytochemical and ultra- structural characterization of vacuoles in patients with Hurler's disease and investigation of these vacuoles during their development in tissue culture cells or during their disappearance on treatment of tissue culture cells will be studied and the source of the accumulating mucopolysaccharide will be investigated. Methods of immunostaining will be employed to localize and characterize immune globulins in Hodgkin's disease and lymphomas. The development of lesions in stomachs of patients with ulcerative disease will be studied by histochemical methods for mucosubstances.